Lung diseases, such as pneumonitis, pulmonary fibrosis or pulmonary sarcoidosis, affect millions of Americans and others worldwide every year. Those afflicted with these pathological pulmonary conditions can feel short of breath, unable to breath, and may die as a result of these diseases.
Author Silas Kane writes of these diseases that:                “The patient always feels like he . . . needs air and is not getting it. It is a slow, torturous death for the patient. Their last months are spent fighting for every breath they take. Caregivers can stand by helplessly watching their loved ones slowly suffocate to death.”        
See Kane, http://blogcritics.org/archives/2005/09/28/012939.php (Oct. 18, 2006).
Additionally, a significant number of cancer patients receiving bleomycins, such as BLENOXANE® (Bristol-Myers Squib Co., Princeton, N.J.), during chemotherapy develop pulmonary pneumonitis and pulmonary fibrosis after bleomycin administration. Together these pulmonary diseases have significant health and economic impacts. Yet, despite advances in many areas of medicine, comparatively few treatment options and effective therapies are available for these diseases.
Interleukin-16 (IL-16; SEQ ID NO: 2) is a pro-inflammatory cytokine that induces positive chemotaxis of T-lymphocytes, monocytes, eosinophils, and dendritic cells (67 J. Leukocyte Biol. 757 (2000)). IL-16 stimulus also increases IL-1b expression, increases IL-6 expression, and increases IL-15 expression in IL-16 responsive eukaryotic cells (67 J. Leukocyte Biol. 757 (2000)).
IL-16 peptide chain monomers are formed by the Caspase-3 mediated proteolytic processing of a larger 14 kDa precursor molecule (273 J. Biol. Chem. 1144 (1998)). IL-16 monomers form tetrameric peptide chain complexes. These tetrameric IL-16 complexes are believed to be the bioactive form of IL-16 (67 J. Leukocyte Biol. 757 (2000)). Eukaryotic cells that produce IL-16 include cells that express CD4 or CD8, such as T-cells, mast cells, eosinophils, dendritic cells, epithelial cells, fibroblasts, and cells of the cerebellum (67 J. Leukocyte Biol. 757 (2000)). Eukaryotic cells responsive to IL-16 express the CD4 and CD9 peptide chains, but the response to IL-16 may also be independent of these peptide chains (see e.g. 164 J. Immunol. 4429 (2000)).
IL-16 has been reported to play an important role in such diseases as asthma, atopic dermatitis, and rheumatoid arthritis, among others (see e.g. 162 Am. J. Respir. Crit. Care Med. 105 (2000); 109 J. Allergy Clin. Immunol. 681 (2002); 31 J. Rheumatol. 35 (2004). For example, in human patients IL-16 has been shown to be responsible for attracting some asthma inducing cells to the lungs and to play a critical role in triggering asthmatic responses in patients (162 Am. J. Respir. Crit. Care Med. 105 (2000)).
Importantly, the production of cytokines, such as IL-16, may represent a crucial step in promoting the inflammatory immune response and the pulmonary pathologies associated with pneumonitis, pulmonary fibrosis and pulmonary sarcoidosis. However, it has been unclear what, if any, role IL-16 activity plays in these disease conditions.
Thus, a need exists to understand the role of IL-16 in these pathological pulmonary conditions and exploit this role to develop effective treatments for these lung diseases.